Drug Delivery Letters - Volume 12, Issue 1, 2022

Onychomycosis is an infection caused by a fungus that causes discoloration and thickening of the nail layer, and it is the most common nail infection in the world. Trichophyton rubrum and Trichophyton mentagrophytes var. interdigital is the most common anthropophilic dermatophytes that trigger it. Onychomycosis is caused by yeasts such as Candida albicans and Candida parapsilosis, as well as moulds such as Aspergillus spp. Treatment is determined by the type of nail invasion, the fungus genus, and the number of nails affected. Approaches towards conventional methods showed certain drawbacks, which emphasizes the need for alternate approaches to produce better therapeutic efficacy of a product. The present review focused on reporting an updated classification of Onchyomycosis, causative organisms, factors influencing drug permeation, novel treatment strategies for Onychomycosis, and drug permeation enhancement methods.

Background: Despite the vast utility of polymeric nanocarriers in drug delivery, their promising role in formulating efficient transdermal drug delivery systems for managing various diseases has not been explored properly. Introduction: Polymeric nanocarriers have increased the interest of researchers with respect to improving intradermal and transdermal delivery of drugs having ominous penetration and solubility issues. Therefore, a range of invasive and noninvasive approaches have been extensively explored in transdermal delivery systems for the safe and effective transportation of drugs across the skin into the systemic circulation. Accordingly, this review emphasizes the recently used, effectively applicable invasive and noninvasive methodologies for formulating transdermal systems in the form of polymeric films/patches, microneedles, and nanocarriers for better penetration and bioavailability. Conclusion: Various novel methodologies for transdermal drug delivery systems offer countless benefits over conventional methods, but still, a safe and effective delivery system is the major challenge in terms of reproducible pharmacokinetic and pharmacodynamic results.

Background: Gene therapy is a promising approach for the treatment of various diseases, including cancer, hereditary disorders, and some viral infections. The development of efficient and safe gene delivery systems is essential for facilitating gene transfer to various organs and tissues in vivo. Objective: In this review, we briefly describe the principal mechanisms of gene delivery systems, particularly electroporation, and discuss the latest advancements in the application of electroporation for in vivo gene transfer. Methods: A narrative review of all the relevant publication known to the authors was conducted. Results: In recent years, electroporation-based strategies have emerged as an auspicious and versatile platform for efficient and controlled delivery of various biomolecules, including nucleic acids. Applying electric pulses of enough magnitude leads to the formation of hydrophilic pores in the cell membrane and allows the entry of otherwise membrane-impermeant molecules, such as DNA. Although electroporation has been initially developed for in vitro transfection of cells, it has recently advanced to preclinical in vivo applications and finally to clinical trials. Conclusion: Electroporation has already entered the clinical practice for antitumor therapy and may be an essential part of future personalized treatments. Given the ability of electroporation to deliver multiple genes in a single event, it will also certainly be further developed both as a stand-alone delivery approach and when coupled with other technologies.

Background and Objectives: The present study unveils a simple but innovative combination of existing treatments of three different domains with unique logical aspects. Joint pain is the major cause of disability, especially for older adults. Currently, two widely practiced treatment options are combined to produce simultaneous treatments that overcome the drawbacks of individual treatment and improve patient compliance. Moreover, a third treatment option of cooling and counterirritant material (Menthol) for pain relief was also explored successfully as a substitute treatment. Methods: In the present study, we formulated and optimized an adhesive topical patch of the model drug diclofenac sodium, a widely used medicine for pain relief and menthol, a cooling and counterirritant substance to aid pain relief. Combinations of two polymers, PVP-K30 and PVA, selected by trial batches, were further optimized by applying a 3x2 full factorial design. Two factors, X1 (PVPK30) and X2 (PVA), were optimized using three responses, R1 (Q2), R2 (Q4), and R3 (Q12). Derived mathematical models for responses were validated using checkpoint batches. The final optimized batch was derived based on the desirability function. Factorial batches were also evaluated for relevant parameters. Results: Results obtained by checkpoint batches were in line with the experimental results with 5% relative error, revealing that the derived models were valid for the design. The final optimized batch obtained by the desirability function followed all set criteria. Medicated patch prepared by optimized formulation was incorporated into the knee brace using an in-house patch holder mechanism. Conclusion: Combined treatment offers better patient compliance for the patient and the healthcare provider, which can be extended to other pain-relieving supportive treatments like elbow braces, waist brace, back support belt, cervical brace, etc.

Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 disease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study. Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were determined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand efficiency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison. Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were identified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be -7.5 and -8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharmacokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were consonant with the many accepted rules and the criteria of drug-likeness. Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease.

Background: In this research study, an attempt has been made using Box-Behnken design (BBD) Response Surface Methodology to find optimized formulation variables at 3 levels (low, medium, and high) to affect the dependent response, which is the % drug release pattern at different time intervals in extending drug release of Benidipine Hydrochloride(BH) matrix tablets. BH extended-release tablets reduce the side effects of multiple dosing used during conventional tablets. Methods: As in the preliminary work, we have found the most profound formulation factors for extending drug release of BH matrix tablets are Eudragit RS 100 amount (X1), HPMC K 100 M (X2), chitosan amount (X3), which we selected as independent factors at their low and high levels for this study considering % drug release at three different time intervals i.e., R1 (% of drug release in 2 hours), R2 (% of drug release in 15 hours) and R3 (% of drug release in 18 hours) as dependent variables using a dissolution media of phosphate buffer pH of 6.8 with 75rpm. Results: From the experimental runs of prepared tablets as predicted by the Design-Expert software, the model shows a quadratic equation due to less p-value, and a very less difference was observed between adjusted R² and predicted values R² in all selected responses, which we considered as the % drug release. Conclusion: Therefore, by using the graphical response surface plot of BBD software, the optimized formulation of BH extended-release tablet of Eudragit RS 100, HPMC K 100 M, and Chitosan containing an amount of 45mg, 105 mg, and 45.71 mg, respectively shows an extended drug release of more than 18 hours. To construct a satisfying fit of the model for the optimized formulation, a result analysis was carried out for the internally studentized residuals versus the experimental runs indicating all data points were placed within limits, and the values of the predicted and actual response of each run were normally distributed near a straight line.

Background: Stattic offers a unique inhibitory effect on the STAT3 signaling pathway, a crucial mechanism in the progression of metastatic cancer. However, the development of Stattic has been impeded by its hydrophobicity and lack of specificity. To overcome these limitations, encapsulation of Stattic with polymeric micelles was previously attempted, which led to a significant increase in the potency of Stattic on breast cancer cell lines. The presence of albumin was believed to contribute to such enhancement, as the protein corona layer formation helps retain the micellar structure before eventual uptake by the cells. Moreover, a previous study had reported the unique affinity of Stattic towards albumin molecule. Objective: This study aimed to explore the integration of Stattic in albumin-based nanoparticles and to assess the in vitro effects. Methods: Albumin/Stattic nanoparticles were prepared by crosslinking with glutaraldehyde. Results: The yielded nanoparticles were 150.0 ± 6.6 nm in size, with ~53% entrapment efficiency. The cumulative release of Stattic in a tumoric acidic environment (pH 5.3; 59%) was 2.6-fold more than neutral environment (pH 7.4; 23%). In blood plasma, 7% cumulative release was observed. The mathematical modeling of the release kinetics revealed that the albumin/Stattic nanoparticles in phosphate buffer saline and plasma followed Korsmeyer-Peppas and Higuchi models, respectively. Among the two cell lines tested, metastatic MDA-MB-231 cells were more sensitive to entrapment of Stattic with albumin nanoparticles, as the IC50 value decreased by 2.5-fold compared to free Stattic. Conclusion: This study reports the formation of low immunogenic and cost-efficient albumin nanoparticles to improve the delivery of Stattic.